Dual role of Monocyte-derived Dendritic Cell in Trypanosoma cruzi Infection

PONCINI CV; GONZALEZ CAPPA STELLA M

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2017

0014-2980

Pathogens can cause inflammation when inoculated into the skin. The vector-transmitted protozoan parasite Trypanosoma cruzi induces poor cellular-infiltration and disseminates, causing high mortality in the experimental model. Here, we characterized the inflammatory foci at the parasite inoculation site and secondary lymphoid organs. While no macrophages and few neutrophils and monocytes (Mo) were recruited into the skin, infection elicited the mobilization of Ly6C+ Mo to draining lymph nodes and spleen. Over time, this population became enriched in CD11b+Ly6C+CD11c+MHCII+CD86+ cells resembling inflammatory dendritic cells (DCs). Adoptive transfer of Ly6C+ Mo purified from the bone marrow of CD11cGFP transgenic mice confirmed the monocytic origin of Ly6C+ DCs found in the spleen of infected animals. Isolated Mo-derived cells not only produced TNF and nitric oxide, but also IL-10 and displayed a poor capacity to induce lymphoproliferation. Ablation of Mo-derived cells by 5-fluorouracil confirmed their dual role during infection, limiting the parasite load by inducible nitric oxide synthase-related mechanisms and negatively affecting the development of anti-parasite T-cell response. This study demonstrated that consistent with their antagonistic properties, this cells not only control the parasite spreading but also its persistence into the host.